title: Interleukin-4 deficiency enhances Th1 responses and crescentic glomerulonephritis in mice.
abstract: Evidence suggests that crescentic glomerulonephritis (GN) is due to T helper cell 1 (Th1) directed delayed-type hypersensitivity (DTH)-like injury. As endogenous interleukin (IL)-4, (the pivotal cytokine in Th2 responses) may attenuate Th1 responses in this disease, we compared the development of crescentic GN, induced by a planted antigen, in mice genetically deficient in IL-4 (IL-4-/-) with disease in normal mice (IL-4+/+). IL-4-/- mice developed more severe GN with increased renal impairment (CCr 35 +/- 7 microliters/min vs. 133 +/- 14 microliters/min, P < 0.002) and crescent formation (55.7 +/- 8.4% vs. 4.9 +/- 1.2%, P < 0.002). This was associated with increased glomerular fibrin deposition, glomerular CD4+ T cell infiltration and macrophage recruitment. Systemically, IL-4-/- mice showed an increased antigen specific Th1 response indicated by increased skin DTH, and increased IgG3 and IgG2b. Decreased IgG1 levels indicated a reduced Th2 response. These results demonstrate a protective role for endogenous IL-4 in crescentic GN. They show that IL-4 deficiency promotes crescentic glomerular injury and amplifies local and systemic Th1 responses. They support the hypothesis that crescent formation results from Th1 immune responses to antigens in the glomerulus.
authors.affiliation: Monash University, Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia. richard.kitching@med.monash.edu.au
authors.forename: A R
authors.initials: AR
authors.lastname: Kitching
authors.forename: P G
authors.initials: PG
authors.lastname: Tipping
authors.forename: D A
authors.initials: DA
authors.lastname: Mutch
authors.forename: X R
authors.initials: XR
authors.lastname: Huang
authors.forename: S R
authors.initials: SR
authors.lastname: Holdsworth
mesh_terms: D000818:Animals; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D015847:Interleukin-4 / Q000172:deficiency*; D007678:Kidney Glomerulus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012756:Sheep; D018417:Th1 Cells / Q000502:physiology*
chemical_list: D007074:Immunoglobulin G; D015847:Interleukin-4